A Synthetic Derivative of the Natural Product Rocaglaol Is a Potent Inhibitor of Cytokine-Mediated Signaling and Shows Neuroprotective Activity in Vitro and in Animal Models of Parkinson's Disease and Traumatic Brain Injury

2005 ◽  
Vol 67 (5) ◽  
pp. 1544-1555 ◽  
Author(s):  
T. Fahrig ◽  
I. Gerlach ◽  
E. Horváth
Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 361
Author(s):  
Gabriel Gonzalez ◽  
Jiří Grúz ◽  
Cosimo Walter D’Acunto ◽  
Petr Kaňovský ◽  
Miroslav Strnad

Cytokinins are adenine-based phytohormones that regulate key processes in plants, such as cell division and differentiation, root and shoot growth, apical dominance, branching, and seed germination. In preliminary studies, they have also shown protective activities against human neurodegenerative diseases. To extend knowledge of the protection (protective activity) they offer, we investigated activities of natural cytokinins against salsolinol (SAL)-induced toxicity (a Parkinson’s disease model) and glutamate (Glu)-induced death of neuron-like dopaminergic SH-SY5Y cells. We found that kinetin-3-glucoside, cis-zeatin riboside, and N6-isopentenyladenosine were active in the SAL-induced PD model. In addition, trans-, cis-zeatin, and kinetin along with the iron chelator deferoxamine (DFO) and the necroptosis inhibitor necrostatin 1 (NEC-1) significantly reduced cell death rates in the Glu-induced model. Lactate dehydrogenase assays revealed that the cytokinins provided lower neuroprotective activity than DFO and NEC-1. Moreover, they reduced apoptotic caspase-3/7 activities less strongly than DFO. However, the cytokinins had very similar effects to DFO and NEC-1 on superoxide radical production. Overall, they showed protective activity in the SAL-induced model of parkinsonian neuronal cell death and Glu-induced model of oxidative damage mainly by reduction of oxidative stress.


Author(s):  
Mohammad Zamanian ◽  
Małgorzata Kujawska ◽  
Marjan Nikbakht Zadeh ◽  
Amin Hassanshahi ◽  
Soudeh Ramezanpour ◽  
...  

Background & objective: Neurological diseases are becoming a significant problem worldwide, with the elderly at a higher risk of being affected. Several researchers have investigated the neuroprotective effects of Carvacrol (CAR) (5-isopropyl-2-methyl phenol). This review systematically surveys the existing literature on the impact of CAR when used as a neuroprotective agent in neurological diseases. Methods: The systematic review involved English articles published in the last ten years obtained from PubMed, Google Scholar, and Scopus databases. The following descriptors were used to search the literature: “Carvacrol” [Title] AND “neuroprotective (neuroprotection)” [Title] OR “stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, seizure, epilepsy [Title]. Results: : A total of 208 articles were retrieved during the search process, but only 20 studies met the eligibility criteria and were included for review. A total of 20 articles were identified, in which the efficacy of CAR was described in experimental models of stroke, traumatic brain injury, Parkinson’s disease, Alzheimer’s disease, , epilepsy, and seizure, through motor deficits improvements in neurochemical activity, especially antioxidant systems, reducing inflammation, oxidative stress and apoptosis as well as inhibition of TRPC1 and TRPM7. Conclusion : The data presented in this study support the beneficial impact of CAR on behavioural and neurochemical deficits. CAR benefits accrue because of its anti-apoptotic, antioxidant, and anti-inflammatory properties. Therefore, CAR has emerged as an alternative treatment for neurological disorders based on its properties.


2019 ◽  
Vol 32 (1) ◽  
pp. 46-60 ◽  
Author(s):  
Julie M. Joyce ◽  
Oury Monchi ◽  
Zahinoor Ismail ◽  
Mekale Kibreab ◽  
Jenelle Cheetham ◽  
...  

2017 ◽  
Vol 82 (5) ◽  
pp. 744-754 ◽  
Author(s):  
Alejandra Camacho-Soto ◽  
Mark N. Warden ◽  
Susan Searles Nielsen ◽  
Amber Salter ◽  
David L. Brody ◽  
...  

Author(s):  
Sanjay Manohar ◽  
Valerie Bonnelle ◽  
Masud Husain

Attention deficits are a frequent and particularly disabling consequence of many neurological disorders, from patients with focal brain lesions through to individuals with traumatic brain injury or neurodegenerative conditions, such as Parkinson’s disease. They are often associated with apparent confusion, fatigue, irritability, and increased time and effort to perform even simple everyday tasks, and constitute a real challenge for rehabilitation. In many cases, attention deficits may be crucial factors underlying failures of memory and higher cognitive functions, contributing to difficulties in resuming previous activities and independent daily living. Here the authors first consider four aspects of attention—selective, sustained, executive, and divided—together with brain regions and networks considered to underpin normal attention and disorders of attention. The authors focus on focal brain lesions, traumatic brain injury and Parkinson’s disease as important examples illustrating the effects of different brain pathologies on attention function.


2017 ◽  
Vol 114 (6) ◽  
pp. E1009-E1017 ◽  
Author(s):  
Michele Perni ◽  
Céline Galvagnion ◽  
Alexander Maltsev ◽  
Georg Meisl ◽  
Martin B. D. Müller ◽  
...  

The self-assembly of α-synuclein is closely associated with Parkinson’s disease and related syndromes. We show that squalamine, a natural product with known anticancer and antiviral activity, dramatically affects α-synuclein aggregation in vitro and in vivo. We elucidate the mechanism of action of squalamine by investigating its interaction with lipid vesicles, which are known to stimulate nucleation, and find that this compound displaces α-synuclein from the surfaces of such vesicles, thereby blocking the first steps in its aggregation process. We also show that squalamine almost completely suppresses the toxicity of α-synuclein oligomers in human neuroblastoma cells by inhibiting their interactions with lipid membranes. We further examine the effects of squalamine in a Caenorhabditis elegans strain overexpressing α-synuclein, observing a dramatic reduction of α-synuclein aggregation and an almost complete elimination of muscle paralysis. These findings suggest that squalamine could be a means of therapeutic intervention in Parkinson’s disease and related conditions.


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